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U.S. Department of Health and Human Services

About FDA

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Eculizumab (Soliris)

On September 23, 2011, the U.S. Food and Drug Administration (FDA) granted accelerated approval for the use of eculizumab (Soliris®, Alexion, Inc.) for the treatment of pediatric and adult patients with atypical hemolytic uremic syndrome (aHUS). 

Eculizumab is a monoclonal antibody that inhibits the production of the terminal complement components C5a and the membrane attack complex C5b-9 by binding to complement protein C5. Prevention of the formation of C5a and the terminal complement complex inhibits complement-mediated thrombotic microangiopathy in patients with aHUS. Eculizumab previously received approval for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) in March, 2007. 

Two prospective single arm trials enrolling 37 adult and adolescent patients with aHUS and one retrospective trial of 19 pediatric patients and 11 adult patients with aHUS were reviewed. 

In a prospective trial of adult and adolescent patients (N = 17) with aHUS that was resistant to plasma therapy, eculizumab resulted in elimination of the requirement for dialysis, sustained improvement in the estimated glomerular filtration rate (eGFR), and sustained improvement in hematologic parameters that correlate with aHUS disease activity. Four of the five patients who required dialysis at entry were able to discontinue dialysis for the duration of eculizumab treatment. A median improvement in eGFR of at least 15 ml/min/1.73 m2 was observed in 9 of 17 (53%) patients enrolled for a median duration of 251 days (range: 70-392 days). 

Hematologic normalization (achievement or maintenance of normal platelet counts and LDH levels for at least four weeks) was achieved in 13 of 17 (76%) patients for a median duration of 37 weeks (range: 25, 62+ weeks). These findings were supported by elimination of the requirement for plasma therapy in the majority of patients and improvement in other laboratory markers of hemolysis and evidence for suppression of terminal complement activity.

In the second prospective trial of adult and adolescent patients (N = 20) who required chronic plasma therapy, eculizumab treatment allowed cessation of plasma therapy and maintained renal function, as indicated by stable dialysis requirements and eGFR parameters. A total of 18 of 20 (90%) patients maintained hematologic normalization after discontinuing chronic plasma therapy. The median duration of hematologic normalization was 38 weeks (range: 22 to 52+ weeks).

The outcomes of 19 pediatric patients (median age: 6 years; range: 2 months to 17 years) in a retrospective trial (N = 30) were consistent with the outcomes observed in the prospective studies. Four of eight (50%) pediatric patients who previously required dialysis were able to discontinue dialysis after eculizumab therapy. Additionally, 7 of 19 (37%) pediatric patients exhibited an improvement in eGFR of at least 15 mg/min/1.73 m2, and 8 of 19 (42%) pediatric patients achieved or maintained normal hematologic parameters for at least four weeks. These findings are supported by an elimination of the requirement for plasma therapy in the majority of patients.

The most frequently reported adverse reactions in aHUS single arm prospective trials (≥15% combined per patient incidence) are hypertension, upper respiratory tract infection, diarrhea, headache, anemia, vomiting, nausea, urinary tract infection, and leukopenia.

Treatment with eculizumab is associated with life-threatening and fatal meningococcal infections. To mitigate this risk, a Risk Evaluation and Mitigation Strategy (REMS) has been developed. Health care providers are required to enroll in a registration program, certify that they will counsel and provide educational materials to patients about the risks of eculizumab, and agree to promptly report cases of meningococcal infection. The product labeling contains a boxed warning to inform healthcare providers and patients of the serious risk of meningococcal infection. The boxed warning recommends immunization with a polyvalent meningococcal vaccine.

Children treated with eculizumab may also be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenza type b (Hib). Pediatric patients should also receive vaccinations for the prevention of Streptococcus pneumoniae and Haemophilus influenza type b (Hib) infections according to ACIP guidelines.

The safety and effectiveness of eculizumab has not been established for the treatment of typical hemolytic uremic syndrome, which is usually associated with an infection caused by bacteria producing shiga-toxin.

Eculizumab is administered as an intravenous infusion. The recommended dosing for adult patients with aHUS is 900 mg weekly for the first 4 weeks, followed by 1200 mg weekly one week later, and 1200 mg every 2 weeks thereafter. The dosage regimen for pediatric patients is based upon body weight. Full prescribing information for eculizumab is available at:

http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125166s172lbl.pdf

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).